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. 2022 Aug 30;21:171. doi: 10.1186/s12943-022-01642-5

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© The Author(s) 2022

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

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Fig. 1 — The key genes related to the innate resistance of CDK4/6 inhibitors were explored by analysis of ctDNA derived from patients with breast cancer. A-D Schematic overview of the study design and analytical workflow. PFS: progression-free survival. ctDNA: circulating tumour DNA. ddPCR: droplet digital PCR. IHC: immunohistochemistry. Multi-IF: multiplex immunofluorescence. E The landscape of high-frequency altered genes in plasma from the discovery patient cohort. The plot shows patients with innate resistance or clinical benefit following palbociclib treatment, with individual information about numbers of metastases, treatment lines, and endocrine therapy drugs used in combination with palbociclib. S6K1 (i.e. RPS6KB1) amplification was observed in three patients with innate resistance to palbociclib but not in those with clinical benefit